Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Ketamine for chronic pain –is this a good idea?

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A recent phase 1 study explored the use of oral ketamine for chronic pain (J Pediatr 2013; 163: 194-200).

Ketamine has several mechanisms of actions in improving pain.  It is frequently used in emergency room settings because of its analgesic and dissociative amnestic qualities.  In addition, it has relatively little cardiorespiratory impact, a short half-life, and is better tolerated in children than adults.

Given the frequency of chronic pain in children and the relative paucity of treatment options, the authors aimed to determine whether ketamine in a short-term study (2 weeks) would be safe and effective.  This prospective study enrolled 12 patients who received ketamine 3 times per day at dosages of 0.25-1.5 mg/kg/dose .**

Pain diagnoses included chronic pancreatitis, Crohn’s disease, esophageal spasm, headache, joint pains, and other causes.  Median age was 16 years (range 11-19).

Results:

  • Two participants, both treated with 1.5 mg/kg/dose, experienced dose-limiting toxicities: sedation and anorexia.
  • Of the 12 patients, 5 had improvement in pain scores; 2 of these patients had complete resolution of pain which lasted >4 weeks off ketamine treatment.
  • There was evidence of norketamine accumulation in many patients.  Norketamine is the major metabolite of ketamine.

**Note: All medication dosages should be checked in standard references for individual patients.  This blog may have transcription errors with regard to dosages.

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More breastmilk, better development

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A recent study further explored breastmilk’s effect on infant cognitive and motor development in the French EDEN Mother-Child Cohort Study (J Pediatr 2013; 163: 36-42).

The authors acknowledge that previous studies have shown that breastfed children have  higher scores at tests on cognitive abilities; “however, some authors suggested that these results were due to the difference between the socio-demographic and occupational characteristics of mothers who breastfed and those who did not.”  Though, a large randomized trial (Arch Gen Psychiatry 2008; 65: 578-84) showed convincing data that a  longer duration of exclusive-breastfeeding duration improved children’s cognitive development.

So why did the authors bother with this study? The authors note that few studies have been performed in France where breastfeeding is less common than other European countries and their object of showing a dose-response relationship would further the arguments for causality.

Design: 1387 two-year-olds and 1199 three-year-old children were assessed from the EDEN cohort (2002 pregnancies) which prospectively collected data at birth, 4 months, 8 months,   1 year, and 2 years.

Results:

  • After adjusting for many confounding factors, infants who had breastfed scored 3.7 points higher on the Communicative Development Inventory (CDI) than infants who had never breastfed.
  • Longer breastfeeding duration was associated with better cognitive and motor development in 2- and 3-year-old children.  Each additional month of breastfeeding was associated with an increase of 0.75 CDI points and 1.00 in the Ages and Stages Questionnaire (ASQ).

Take-home message: Most studies, including the present, have shown benefits of breastfeeding on infant development.  In addition, there is likely a dose-response relationship.

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Rethinking top-down treatment?

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Given the effectiveness of biologic therapy and the potential for disease modification, the threshold for “top-down” treatment has been lower at this time as compared with “step-up” treatment.  What about long-term outcomes, does starting soon increase or decrease the likelihood of doing well?  A recent study suggests that “early biologic therapy did not improve disease activity or quality of life” (Inflamm Bowel Dis 2013; 19: 1397-1403).

In this retrospective chart review involving 93 patient’s with Crohn’s disease (between 2004 and 2010), patients whose data was prospectively maintained were categorized into either early biologic therapy or a step-up group. For these patients, the mean age at diagnosis was 28 years.  There were no apparent differences in demographic variables between the groups; however, the early biologic therapy group had higher disease activity and lower quality of life scores at baseline. 20% were current smokers and 61% never smoked.  Disease location was similar in both groups; overall, 35% had ileal disease, 13% colonic disease, 34% ileocolonic, and 7% isolated upper tract disease.

Results:

  • Mean Harvey-Bradshaw index and Short Inflammatory Bowel Disease Questionnaire scores at 3, 6, and 12 months were not different between the groups.
  • Early biologic therapy group had more hospitalizations.
  • No difference in steroid use or surgeries was noted at one year.

Take-home message: This study suggests that differences in outcomes between “top-down” therapy and step-up therapy are more pronounced early in the treatment course but may wane after 1 to 2 years.  However, early biologic therapy “may be a more effective strategy in patients with Crohn’s disease with higher disease activity.”

Relating blog posts:

Biliary Atresia More Common in Preterm Infants

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During my fellowship, one of the faculty presented an abstract indicating that 4 out of 40 preterm infants with cholestasis had significant underlying liver disease in addition to parenteral nutrition associated cholestasis (PNAC).  One of these patients had biliary atresia.  The obvious point was not to assume that the cholestasis was due to the usual suspects found with premature infants.

A recent study indicates that biliary atresia (BA) in Taiwan is more common in preterm infants than in term infants (J Pediatr 2013; 163: 100-3).  The authors identified 197 cases (166 term infants) of BA between 2004-2010. This retrospective study used a nationwide screening for BA (the national stool card registry center database) along with reports from surgeons of the Taiwan Biliary Atresia Study Group.

Results:

  • Annual incidence of BA per 10,000 live births was 1.43 and 2.37 for term and preterm infants respectively.
  • Kasai operation before 60 days occurred in 68.7% of term and 44.4% of preterm infants.  Mean age of Kasai was 52.9 days for term infants and 71.8 for preterm infants.
  • Major congenital anomalies along with BA were more common among preterm (18.5%) than term (4.1%).
  • Mean onset of clay-colored stools among preterm infants was 33.6 days compared with 29.6 for term infants.
  • Stool cards had good sensitivity in detecting BA in both preterm and term infants: 96.3% and 92.8% respectively.
  • Jaundice-free at 3 months following Kasai was 62% of term infants and 37% of preterm infants.
  • 18-month survival with native liver was 72.7% in term infants and 50% in preterm infants.

While the authors point out several studies that have shown prematurity is an independent risk factor associated with BA, nevertheless this idea is counter to conventional wisdom that BA patients are typically well-appearing term infants at the time of diagnosis.  The authors also note that despite delayed diagnosis in preterm infants, this was not correlated with an impact on jaundice-free status 3 months following surgery.  This finding, in particular, should be cautiously interpreted as there were only 27 infants in the preterm group.

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Badmouthing other doctors from NYTimes

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A fascinating piece from the NY Times (nyti.ms/1b1IqCM ) indicates that many physicians are quick to disparage other physicians, even when the care that was provided was appropriate. Below is an excerpt:

Over the last decade, few issues have garnered as much interest among health care experts as disrespectful behavior among doctors. While sociologists have devoted careers to researching the topic, it wasn’t until the 1990s that the medical profession itself began to take serious note.

Spurred on by the increasing complexity of medicine, concerns about safety and patient satisfaction and an ever-growing urgency to contain costs, the Institute of Medicine convened a national panel of health care experts to discuss “the chasm” between what could be and what was actually being done for patients. In 2002, they published an ambitious report that called for a “sweeping redesign of the entire health system.” Realizing that vision, said the panel, would require, among other changes, better collaboration and cooperation among physicians and the creation of a “culture of respect.”

Medical schools, regulatory agencies, professional organizations and entire health care systems responded to this cri de coeur. Official definitions of professionalism were rewritten to incorporate the concepts of teamwork and shared responsibility. Schools added mandatory coursework on thewhys and hows of working in a team. And licensing and accreditation boards began asking for evidence that doctors could not only lead, but that they also knew how to work as part of a team.

But this new study reveals that old habits and responses die hard.

Researchers trained three actors to portray “standardized patients” with advanced lung cancer who had recently moved to town after being treated by another doctor and who remained unsure about their diagnosis or prognosis. The actors, carrying medical records written to reflect only universally accepted guidelines of care, made a total of nearly three dozen office visits to various family physicians and cancer specialists working in the community.

The actors were not told to elicit the doctors’ opinions about their previous care; but after analyzing transcripts from each office visit, the researchers found that in 40 percent of the consultations, doctors went ahead and spontaneously offered their opinion anyway. A tiny percentage of these comments were neutral; a third were supportive. The vast majority, however, were unabashedly critical, with the doctors’ comments ranging from “Hell, you don’t want to trust doctors,” to “This guy’s an idiot!”

“Doctors will throw each other under the bus,” said Susan H. McDaniel, lead author of the study and a professor of psychiatry and family medicine at the University of Rochester Medical Center. “I don’t think they even realize the extent to which they do that or how it can affect patients.”

Probably, added Dr. McDaniel, most of the comments were unintentional. Faced with a constant pressure to cut costs, increase productivity and keep patients happy, plus the additional difficulty in this case of discussing prognosis with a terminal cancer patient, many of the doctors no doubt experienced significant levels of stress. In the moment, criticizing another physician to a patient might have felt like an effective way to fortify their own credentials and build up the patient’s trust.

“There is probably something reassuring in saying, ‘Boy, your doctor didn’t do a good job and now I’m going to take care of you,’” Dr. McDaniel noted. “But those kinds of comments are bad for the patient.”

Injecting steroids for esophageal strictures -does it work?

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A recent report indicates that steroid injections are not effective in patients with cervical anastomotic strictures (Clin Gastroenterol Hepatol 2013; 11: 795-801).

While this double-blind randomized control multicenter study of 60 patients (mean age 63) dealt with a specific subtype of strictures, the implications may be broader.  In this study, all patients had undergone esophectomy with gastric tube reconstruction.  The treatment group had 4 quadrant injections of 0.5 mL (20 mg) of triamcinolone and the control group had saline injections.  After injections, patients had Savary dilation to 16 mm.  Patients were followed for 6 months subsequently.

Results: In the treatment group 45% remained dysphagia-free for 6 months compared with 36% of controls (RR=12.6, p=0.46).  Median number of dilatations was 2 in treatment group compared with 3 in the controls.  One corticosteroid-treated patient developed a probable perforation and was excluded from final analysis. Four patients in the treatment group, and none in controls, developed Candida esophagitis.

No statistically significant decrease in dilatations or symptoms was demonstrated.

In their discussion, the authors review the effects of intraesophageal corticosteroid therapy and previous studies.  “Thus far, RCTs supporting this…are limited and, if available, are only small-sized and not focused on anastomotic strictures.”  According to the discussion, the evidence for steroid injection may be strongest for peptic strictures, primarily based on a small, sham-controlled RCT (Am J Gastroenterol 2005; 100: 2419) which demonstrated lower redilatation rates in this setting.

To prove that steroids would be effective if there was only a 10-20% improvement would take at least 200-750 patients

Take-home message (from authors): the routine use of corticosteroid injections in patients with benign anastomotic strictures cannot be recommended.

Related references:

  • -Refractory strictures (NASPGHAN 2011): =if not >14 mm after 5 sessions.   Complex strictures: >2 cm long, tortuous, or if scope cannot be passed predilatation. Consider Fluoro for complex strictures. Described technique of endoknife if only one-sided stricture which are hard to dilate.
  • -Am J Gastroenterol 2005; 100: 2419.  Double-blind, randomized trial showed benefit of steroid injection for Rx of recalcitrant peptic strictures. Consider triamcinolone along length of stricture; max ~10mg (2-4 mg/injection)
  • -JPGN 2007; 44: 336. n=16 pts. Mitomycin 0.1mg/mL; apply for 2-3min c pledget.
    -JPGN 2006; 42: 437.  Case report of using indwelling balloon for daily dilatation in refractory patients.
  • -Endoscopy. 2006; 38(4):404-7).  Mitomycin C: an alternative conservative treatment for refractory esophageal stricture in children?
  • -JPGN 2005; 41: 35A (pg503).  Use of stents for refractory benign strictures, n=10.
  • -Gastroenterol 1999; 117: 229 & 233. AGA position statement and technical review.

**Dosing regarding triamcinolone or mitomycin C has not been clearly established for esophageal strictures.  Doses listed above are based on my reading of the references but no specific dose is advocated on this posting.

Top Cited 100

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In a recent commentary, the authors provide a list of the most commonly cited digestive disease articles from 1967-2007.  (Gastroenterol 2013; 144: 673-76)

The top three:

  1. Manns, M, et al. Lancet 2001; 358: 958-65. This study compared peginterferon alfa-2b with ribavirin against interferon with ribavirin for hepatitis C
  2. Fried M, et al. NEJM 2002; 347: 975-82. This study examined the use of peginterferon alfa-2a with ribavirin for hepatitis C
  3. Marshall B, Warren J. Lancet 1984; 1: 1311-15.  This study identified a bacteria (now called Helicobacter pylori) as a cause of ulcers and gastritis.

http://dx.doi.org/10.1053/j.gastro.2013.02.013

Cyproheptadine for dyspepsia

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A retrospective open-label study has shown that cyproheptadine can be effective for children with dyspeptic symptoms (J Pediatr 2013; 163: 261-7) –thanks to Mike Hart for suggesting this reference.

Methods: In this study, 80 children (65% female) received cyproheptadine for refractory upper gastrointestinal symptoms, including nausea, early satiety, vomiting, retching after fundoplication, and abdominal pain.  The median age was 9.8 years; 48 children were <12 years.  The median dose was 0.19 mg/kg/day and median duration of treatment was 20 weeks.  All patients had undergone upper endoscopy with biopsy.  Gastric emptying studies were undertaken in 52 patients and antroduodenal manometry in 23 patients.

Results:

  • 33 (41%) had a significant response and symptoms resolved in 11 (14%); thus, 55% in total had improvement
  • In those without response, gastrojejunostomy/jejunostomy was placed in 7 patients, and botulinum toxin intrapyloric injection was undertaken in 3 patients
  • Better responses were more common in children <12 years and in females (P=0.04 and 0.03 respectively)
  • Early vomiting after eating and retching after fundoplication responded more favorably than other symptoms
  • Side effects: somnolence (16%), irritable/behavior change (6%), weight gain (5%)

How does cyproheptadine work? While this is not known, the authors speculate that the antiserotonin effects may improve gastric accommodation.

Take-home message: Cyproheptadine may help dyspeptic symptoms, especially in children <12 years and in those with vomiting and retching after fundoplication.  A prospective study would be helpful too.

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What physicians can learn from fast-food restaurants and retail shops

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Going to a physician is worse than going to a jeweler.  At a jeweler’s, it is commonly said that if you have to ask how much it costs, then you probably cannot afford it.  When seeing a physician, in all likelihood the costs of various tests are not completely known (until the bill arrives).  In contrast, when going to a fast-food restaurant or to most shops, the price is clearly posted and this helps make an informed decision.

Not surprisingly, a recent study from Johns Hopkins has shown that physicians order less tests when the fee for the test was displayed (JAMA Intern Med 2013; 173: 903-08).

This study randomly assigned 61 inpatient diagnostic laboratory tests to an “active” arm with the fee displayed or to a control arm with no fee displayed.  The displayed fee was based on the Medicare.  During a 6-month baseline period 208-2009, no fees were displayed.  allowable fee.  Pediatrics was one of the smallest hospital services involved in this study (0.8%); internal medicine service accounted for 52.1% and intensive care 26.6%.

Results: Rates of test ordering were reduced from 3.72 tests per patient-day in baseline period to 3.40 tests per patient-day in the intervention period (8.59% decrease).  In contrast, the control arm tests increased during the same period from 1.15 to 1.22 (5.64% increase).  The net result was $400,000 charge reduction in a 6-month period.

The study limitations included the practice setting where most orders are placed by residents. In addition, it is not known whether the reductions in testing led to any detrimental affects.

Trying to sort out the price of laboratory tests, imaging, and procedures for the individual are complicated by the unfathomable world of insurance contracting and discounts. Yet, providing the baseline cost, even without knowing what part insurance would cover, would be worthwhile.  Presumably, somebody is paying.

Bottomline: How many physicians know how much that blood test, the endoscopy, or the CT scan is going to cost? In medicine, physicians frequently discuss risk-benefit ratio.  I think an effort to understand the cost should be part of the equation as well.

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More data on DILI

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Using a population-based cohort, the authors of a recent study from Iceland performed a prospective study, collecting data on 96 individuals with drug-induced liver injury (DILI) from 2010-2011 (Gastroenterol 2013; 144: 1419-25 & editorial 1335-36).  This study benefitted from a centralized medical care system with about 250,000 adults.  Patients with acetaminophen toxicity were excluded.

Results:

  1. DILI occurred in 19 cases per 100,000 persons per year.  This is higher than previous DILI estimates in other populations and may be due to identifying more subclinical cases.
  2. DILI increased markedly with age from 9 per 100,000 among 15-29 year olds to 41 per 100,000 among those >70; however, this paralleled the increase use of medications.
  3. Eight drugs were implicated in more than 1 case with subsequent risk estimates:
  • Augmentin 1 per 2350 users
  • Azathioprine 1 per 133  (mostly anicteric cases)
  • Infliximab 1 per 148
  • Nitrofurantoin 1 per 1369
  • Isotretinoin 1 per 732
  • Atorvastatin 1 per 3693
  • Diclofenac 1 per 9148
  • Doxycycline 1 per 16,339

Some commonly implicated drugs did not show up on the list: fluoroquinolones, macrolide antibiotics, minocycline, valproic acid, and cancer chemotherapeutic agents (except one case due to imatinib).  The editorialist notes that these agents are not commonly used in Iceland.  Also, 16% of cases were due to herbals and dietary supplements.

Consequences of DILI: 27% developed jaundice, 12% required hospitalization, and 1 patient died.  The median time for liver tests to normalize in those that recovered was 64 days.

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